Potassium Carbonate → Toluene-4-sulfonic acid 8-(2-chloro-phenyl)-6-fluoro-chroman-2-ylmethyl ester

HRID 902312

반응식

HRID 902312 반응식
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([O:11][CH2:12][CH:13]2[CH2:22][CH2:21][C:20]3[C:15](=[C:16](Br)[CH:17]=[C:18]([F:23])[CH:19]=3)[O:14]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[Cl:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1B(O)O.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.CC1C(P(C2C(C)=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.CC1C(P(C2C(C)=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.Cl[Pd]Cl>[Cl:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[C:16]1[CH:17]=[C:18]([F:23])[CH:19]=[C:20]2[C:15]=1[O:14][CH:13]([CH2:12][O:11][S:8]([C:5]1[CH:4]=[CH:3][C:2]([CH3:1])=[CH:7][CH:6]=1)(=[O:9])=[O:10])[CH2:22][CH2:21]2

참가 물질

7

반응물 3

HCID 11430Potassium CarbonateHCID 27343222-Chlorophenylboronic acidHCID 86609108(8-bromo-6-fluoro-3,4-dihydro-2H-chromen-2-yl)methyl 4-methylbenzenesulfonate

생성물 1

HCID 86609109Toluene-4-sulfonic acid 8-(2-chloro-phenyl)-6-fluoro-chroman-2-ylmethyl ester수율 71.2%

시약·촉매·용매 3

HCID 10876480Bis(tri-o-tolylphosphine)palladium(II) Dichloride촉매HCID 962Water용매HCID 312751,4-Dioxane용매

실험 절차

To a solution of (8-bromo-6-fluoro-3,4-dihydro-2H-chromen-2-yl)methyl 4-methylbenzenesulfonate (0.33 g, 0.795 mmol) and 2-chlorophenylboronic acid (249 mg, 1.589 mmol) in dioxane (9 mL) was added a solution of potassium carbonate (329 mg, 2.38 mmol) in water (3 mL) and the mixture purged with nitrogen for 20 minutes. Trans-dichlorobis(tri-o-tolylphosphine)palladium (II) (31.2 mg, 0.0397 mmol) was added and the reaction mixture heated to reflux for 18 hours. The cooled reaction mixture was then partitioned between ethyl acetate (100 mL) and 2.0 M aqueous sodium hydroxide (100 mL). The organic layer was separated, washed with water (100 mL) and saturated brine (100 mL), dried over magnesium sulfate, filtered and concentrated under reduced pressure to afford a yellow syrup. Purification by flash chromatography using a solvent gradient of 5 to 20% ethyl acetate in hexane gave 253 mg (71%) of toluene-4-sulfonic acid 8-(2-chloro-phenyl)-6-fluoro-chroman-2-ylmethyl ester as a colorless syrup. MS (ESI) m/z 464 ([M+NH4]+).

후처리

  1. customthe mixture purged with nitrogen for 20 minutes
  2. temperaturethe reaction mixture heated
  3. temperatureto reflux for 18 hours
  4. customThe cooled reaction mixture
  5. customwas then partitioned between ethyl acetate (100 mL) and 2.0 M aqueous sodium hydroxide (100 mL)
  6. customThe organic layer was separated
  7. washwashed with water (100 mL) and saturated brine (100 mL)
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customto afford a yellow syrup
  12. customPurification by flash chromatography

출처 및 근거

ORD 기록
ord-231dbad2696d49acb8cc0f1d4c9009eb
출처 데이터셋
uspto-grants-2008_04
특허 번호
US07365095B2

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